Precision medicine requests preferential transportation of the pharmaceutical substances to the pathological site and impartation of localized therapeutic activities to the targeted cells. To accomplish this goal, we attempted a facile nanoscaled ultrasound-responsive delivery system, characterized by doxorubicin assembled with an amphiphilic copolymer (multiple of hydrophobic stearic segments tethered onto the hydrophilic pullulan backbone through ultrasound-labile oxyl-alkylhydroxylamine linkage). As a consequence of the strategically installed ultrasound-labile oxyl-alkylhydroxylamine linkage to elicit the tailored segregation of the hydrophilic pullulan and the hydrophobic stearic segments upon ultrasound impetus, the constructed nanoscaled self-assembly presented distinctive structural destabilization behaviors and afforded spatiotemporal controlled liberation of the cytotoxic drugs. It is worthy to note that the ultrasound was determined to markedly lower the IC₅₀ of the proposed system from over 10 μg/mL to 2.33 μg/mL (approximate 4-fold), thereby serving as a facile impetus to amplify the cytotoxic potency of the proposed drug delivery vehicles. Furthermore, drastic tumor ablation was validated by dosage of the proposed doxorubicin delivery system to T41 tumor-bearing mice accompanied by the tumor-localized ultrasound impetus, while no observable adverse side effect was confirmed. Therefore, the results advocated our ultrasound-responsive delivery vehicle as a tempting strategy for precise spatiotemporal control of the release of the drug cargo, thus affording selectively amplified cytotoxic potency to the ultrasound-imposed site, which should be highlighted as important progress toward precision medicine.

中文翻译：

---

超声响应纳米颗粒用于消融实体瘤的化学治疗效能的选择性放大

精密医学要求将药物优先运输到病理部位，并将局部治疗活性赋予靶细胞。为了实现这个目标，我们尝试了一种简便的纳米级超声响应性递送系统，其特征是将阿霉素与两亲共聚物组装在一起（通过疏水性不强的羟烷基烷基羟胺键将多个疏水性硬脂酸链段束缚在亲水性支链淀粉主链上）。由于策略性地安装了对超声不稳定的氧基-烷基羟胺键，从而在超声驱动下引发了亲水支链淀粉和疏水性硬脂酸片段的特定分离，所构建的纳米级自组装表现出独特的结构失稳行为，并提供了时空控制的细胞毒性药物的释放。值得一提的是，超声波被确定可以显着降低IC所建议系统中的₅₀种从超过10μg/ mL到2.33μg/ mL（约4倍），从而充当了促进所建议药物递送载体的细胞毒性潜能的推动力。此外，通过将拟议的阿霉素递送系统剂量给药于T41荷瘤小鼠并伴有肿瘤定位的超声刺激，可以证实剧烈的肿瘤消融，但未确认可观察到的不良副作用。因此，结果提倡将我们的超声响应性运载工具作为一种诱因策略，以精确地时空控制药物的释放，从而为超声施加的部位提供选择性放大的细胞毒性，这应被强调为朝着精确医学发展的重要进展。